ABSTRACT This is a competitive renewal application for U01-AA015134. The history, experience, existing infrastructure, and experienced staff and collaborators of our South African (SA) fetal alcohol spectrum disorders (FASD) research program present unique opportunities to better define population-based characteristics of children with FASD and their mothers. Furthermore, the opportunity to pursue innovative explorations into etiology of FASD in the coming five years is excellent. We will simultaneously pursue three diverse, but complementary, aims. Aim 1: Screen women of childbearing age drinking in prenatal clinics for high risk drinking and continuing study of maternal risk. While there are multiple reasons for screening, in Aim 1 the purpose is for selective (secondary) prevention of FASD. We will initiate a case control efficacy study (n=400) of the use of one-session motivation enhancement therapy (MET) in prenatal clinics. These prevention activities follow from findings and experience in previous prevention efforts. Continuing prevention activities in antenatal clinics will also facilitate recruitment of participants for cutting-edge biomarker studies in Aim 3. Aim 2: Continue longitudinal studies of the trajectory of FASD in the early years of life in two established cohorts. We will continue regularly-scheduled, follow-up evaluation of the physical growth and cognitive/behavioral trajectory in an established cohort of 197 diagnosed children ages 6-11 years and their mothers. We will also pursue similar developmental monitoring of a second maternal/child cohort (n= ~230 dyads) recruited over the past 2 years. Cohort 2 will be finalized in October, 2017. A nested study of sMRI measurement will also be undertaken in a sub-sample of Cohort 1. Aim 3: Collect appropriate biological samples for assessing the validity and utility of alcohol use biomarkers and markers of the role of nutrition and nutrition genetics to better assess the interactive role of nutrition and prenatal alcohol use in severity of child outcomes and the etiology of FASD. We will assess alcohol use via two biomarkers, ethyl glucuronide (EtG) and phosphatidylethanol (PEth) in antenatal clinics and prevention initiatives for accurate assessment in both longitudinal research and monitoring prevention. Self-reported alcohol use by quantity, frequency, and gestational timing (QFT) and the AUDIT will serve as comparison data. We will also collect samples and data for analyzing the role of nutritional components in affecting child outcomes via a combination of: dietary intake surveys; evaluation of multiple micronutrients in plasma samples from of pregnant women; analysis of genetic polymorphisms (SNPs) influential in metabolism, absorption, and regulation of essential nutrients.